Wnt Signaling Networks in Autism Spectrum Disorder and Intellectual Disability Vickie Kwan, Brianna K
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Β-Catenin Confers Resistance to PI3K and AKT Inhibitors and Subverts Foxo3a to Promote Metastasis in Colon Cancer
β-catenin Confers Resistance to PI3K and AKT inhibitors and Subverts FOXO3a to Promote Metastasis in Colon Cancer Stephan P. Tenbaum1§, Paloma Ordóñez-Morán2§#, Isabel Puig1§, Irene Chicote1, Oriol Arqués1, Stefania Landolfi3, Yolanda Fernández4, José Raúl Herance5, Juan D. Gispert5, Leire Mendizabal6, Susana Aguilar7, Santiago Ramón y Cajal3, Simó Schwartz Jr4, Ana Vivancos6, Eloy Espín8, Santiago Rojas5, José Baselga9, Josep Tabernero10, Alberto Muñoz2, Héctor G. Palmer1* 1 Vall d’Hebrón Institut d´Oncología (VHIO). Stem Cells and Cancer Laboratory. Barcelona, Spain. 2 Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain. 3 Department of Pathology, Hospital Universitari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain. 4 Group of Drug Delivery and Targeting, CIBBIM-Nanomedicine and Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Hospital Universitari Vall d’Hebrón, Institut de Recerca Vall d’Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain. 5 Parc de Recerca Biomèdica de Barcelona (PRBB), Centre d´Imatge Molecular (CRC) Corporació Sanitària, Barcelona, Spain. 6 Vall d’Hebrón Institut d´Oncología (VHIO). Genomics Cancer Group. Barcelona, Spain. 7 Centre for Respiratory Research, Rayne Institute, University College London, London, United Kingdom, Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom. 8 General Surgery Service, Hospital Universitari Vall d'Hebrón, Barcelona, Spain. 9 Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, USA; Howard Hughes Medical Institute, Chevy Chase, USA. 10 Medical Oncology Department, Hospital Universitari Vall d'Hebrón, Barcelona, Spain. # Swiss Institute for Experimental Cancer Research, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
DISC1 a Key Molecular Lead in Psychiatry and Neurodevelopment: No-More Disrupted-In-Schizophrenia 1
Molecular Psychiatry (2016) 21, 1488–1489 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1359-4184/16 www.nature.com/mp NEWS AND COMMENTARY DISC1 a key molecular lead in psychiatry and neurodevelopment: No-More Disrupted-in-Schizophrenia 1 M Niwa1, T Cash-Padgett1,4, K-I Kubo2,4, A Saito1,4, K Ishii1,4, A Sumitomo3, Y Taniguchi1, K Ishizuka1, H Jaaro-Peled1, T Tomoda3, K Nakajima2, A Sawa1 and A Kamiya1 Molecular Psychiatry (2016) 21, 1488–1489; doi:10.1038/ second, although DISC1 is a multifunctional intracellular hub mp.2016.154; published online 6 September 2016 protein, we still do not know which specific function of DISC1 underlies each endophenotype or phenotype in mental conditions. Since the middle of the past century, we have serendipitously To address the first question on genetic validity, Sullivan7 come across treatment regimens that can partially ameliorate pointed out that DISC1 is unlikely to be an important ‘genetic’ psychosis and depression. Nonetheless, the mechanisms under- factor for schizophrenia defined by the Diagnostic and Statistical lying such severe mental conditions still remain elusive. Such lack Manual of Mental Disorders (DSM). This discussion is fairly valid, of mechanistic insight into major mental illnesses has hampered and we agree with this statement and conclude as ‘No-More the establishment of precise diagnostic framework, precluding Disrupted-in-Schizophrenia 1.’ Regarding the second question, Tsuboi further discovery of fundamental treatments for these disorders. et al.8 have recently encouraged the field to reinforce the evidence Meanwhile, understanding of the brain at the molecular level that supports the role for DISC1 in early development. -
Circular RNA Hsa Circ 0005114‑Mir‑142‑3P/Mir‑590‑5P‑ Adenomatous
ONCOLOGY LETTERS 21: 58, 2021 Circular RNA hsa_circ_0005114‑miR‑142‑3p/miR‑590‑5p‑ adenomatous polyposis coli protein axis as a potential target for treatment of glioma BO WEI1*, LE WANG2* and JINGWEI ZHAO1 1Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033; 2Department of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China Received September 12, 2019; Accepted October 22, 2020 DOI: 10.3892/ol.2020.12320 Abstract. Glioma is the most common type of brain tumor APC expression with a good overall survival rate. UALCAN and is associated with a high mortality rate. Despite recent analysis using TCGA data of glioblastoma multiforme and the advances in treatment options, the overall prognosis in patients GSE25632 and GSE103229 microarray datasets showed that with glioma remains poor. Studies have suggested that circular hsa‑miR‑142‑3p/hsa‑miR‑590‑5p was upregulated and APC (circ)RNAs serve important roles in the development and was downregulated. Thus, hsa‑miR‑142‑3p/hsa‑miR‑590‑5p‑ progression of glioma and may have potential as therapeutic APC‑related circ/ceRNA axes may be important in glioma, targets. However, the expression profiles of circRNAs and their and hsa_circ_0005114 interacted with both of these miRNAs. functions in glioma have rarely been studied. The present study Functional analysis showed that hsa_circ_0005114 was aimed to screen differentially expressed circRNAs (DECs) involved in insulin secretion, while APC was associated with between glioma and normal brain tissues using sequencing the Wnt signaling pathway. In conclusion, hsa_circ_0005114‑ data collected from the Gene Expression Omnibus database miR‑142‑3p/miR‑590‑5p‑APC ceRNA axes may be potential (GSE86202 and GSE92322 datasets) and explain their mecha‑ targets for the treatment of glioma. -
ANK3 As a Risk Gene for Schizophrenia: New Data in Han Chinese And
RESEARCH ARTICLE Neuropsychiatric Genetics ANK3 as a Risk Gene for Schizophrenia: New Data in Han Chinese and Meta Analysis Aihua Yuan,1 Zhenghui Yi,1 Qiang Wang,2 Jinhua Sun,1 Zhiqiang Li,3 Yasong Du,1 Chen Zhang,1 Tao Yu,3 Juan Fan,1 Huafang Li,1 and Shunying Yu1* 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China 2Mental Health Center Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China 3Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, P.R. China Manuscript Received: 13 December 2011; Manuscript Accepted: 4 October 2012 Histological and neuroimaging evidence supports the hypothesis that neuronal disconnectivity may be involved in the pathogenesis How to Cite this Article: of schizophrenia. A genome-wide association study (GWAS) Yuan A, Yi Z, Wang Q, Sun J, Li Z, Du Y, showed a single nucleotide polymorphism (SNP), rs10761482 in Zhang C, Yu T, Fan J, Li H, Yu S. 2012. ANK3 ANK3 ankyrin 3 ( ), a major neuron-enriched gene, was associated as a Risk Gene for Schizophrenia: New Data in with schizophrenia although inconsistent results had been Han Chinese and Meta Analysis. reported. Two meta analyses reported another SNP rs10994336 Am J Med Genet Part B 159B:997–1005. in ANK3 gene confers risk to bipolar disorder (BD). Due to evidence of genetic overlap between schizophrenia and BD, we investigated common findings by analyzing the association of ANK3 polymorphisms (rs10761482, rs10994336, and two mis- from family, adoption, and twins studies supported high herit- senses, rs3808942 and rs3808943) with schizophrenia, using the ability in the development of schizophrenia (80%). -
The TRAX, DISC1, and GSK3 Complex in Mental Disorders and Therapeutic Interventions Yu-Ting Weng1,2, Ting Chien1, I-I Kuan1 and Yijuang Chern1,2*
Weng et al. Journal of Biomedical Science (2018) 25:71 https://doi.org/10.1186/s12929-018-0473-x REVIEW Open Access The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions Yu-Ting Weng1,2, Ting Chien1, I-I Kuan1 and Yijuang Chern1,2* Abstract Psychiatric disorders (such as bipolar disorder, depression, and schizophrenia) affect the lives of millions of individuals worldwide. Despite the tremendous efforts devoted to various types of psychiatric studies and rapidly accumulating genetic information, the molecular mechanisms underlying psychiatric disorder development remain elusive. Among the genes that have been implicated in schizophrenia and other mental disorders, disrupted in schizophrenia 1 (DISC1) and glycogen synthase kinase 3 (GSK3) have been intensively investigated. DISC1 binds directly to GSK3 and modulates many cellular functions by negatively inhibiting GSK3 activity. The human DISC1 gene is located on chromosome 1 and is highly associated with schizophrenia and other mental disorders. A recent study demonstrated that a neighboring gene of DISC1, translin-associated factor X (TRAX), binds to the DISC1/GSK3β complex and at least partly mediates the actions of the DISC1/GSK3β complex. Previous studies also demonstrate that TRAX and most of its interacting proteins that have been identified so far are risk genes and/or markers of mental disorders. In the present review, we will focus on the emerging roles of TRAX and its interacting proteins (including DISC1 and GSK3β) in psychiatric disorders and the potential implications for developing therapeutic interventions. Keywords: TRAX, DISC1, GSK3β, Mental disorders, DNA damage, DNA repair, Oxidative stress, A2AR, PKA Background DNA repair) by interacting with various proteins [4–12]. -
HCC and Cancer Mutated Genes Summarized in the Literature Gene Symbol Gene Name References*
HCC and cancer mutated genes summarized in the literature Gene symbol Gene name References* A2M Alpha-2-macroglobulin (4) ABL1 c-abl oncogene 1, receptor tyrosine kinase (4,5,22) ACBD7 Acyl-Coenzyme A binding domain containing 7 (23) ACTL6A Actin-like 6A (4,5) ACTL6B Actin-like 6B (4) ACVR1B Activin A receptor, type IB (21,22) ACVR2A Activin A receptor, type IIA (4,21) ADAM10 ADAM metallopeptidase domain 10 (5) ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (4) ADCY2 Adenylate cyclase 2 (brain) (26) AJUBA Ajuba LIM protein (21) AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 (4) Akt AKT serine/threonine kinase (28) AKT1 v-akt murine thymoma viral oncogene homolog 1 (5,21,22) AKT2 v-akt murine thymoma viral oncogene homolog 2 (4) ALB Albumin (4) ALK Anaplastic lymphoma receptor tyrosine kinase (22) AMPH Amphiphysin (24) ANK3 Ankyrin 3, node of Ranvier (ankyrin G) (4) ANKRD12 Ankyrin repeat domain 12 (4) ANO1 Anoctamin 1, calcium activated chloride channel (4) APC Adenomatous polyposis coli (4,5,21,22,25,28) APOB Apolipoprotein B [including Ag(x) antigen] (4) AR Androgen receptor (5,21-23) ARAP1 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (4) ARHGAP35 Rho GTPase activating protein 35 (21) ARID1A AT rich interactive domain 1A (SWI-like) (4,5,21,22,24,25,27,28) ARID1B AT rich interactive domain 1B (SWI1-like) (4,5,22) ARID2 AT rich interactive domain 2 (ARID, RFX-like) (4,5,22,24,25,27,28) ARID4A AT rich interactive domain 4A (RBP1-like) (28) ARID5B AT rich interactive domain 5B (MRF1-like) (21) ASPM Asp (abnormal -
Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations
Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations by Jelena Perovanovic M.S. in Molecular Biology and Physiology, September 2009, University of Belgrade M.Phil. in Molecular Medicine, August 2013, The George Washington University A Dissertation submitted to The Faculty of The Columbian College of Arts and Sciences of The George Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 31, 2015 Dissertation directed by Eric P. Hoffman Professor of Integrative Systems Biology The Columbian College of Arts and Sciences of The George Washington University certifies that Jelena Perovanovic has passed the Final Examination for the degree of Doctor of Philosophy as of May 5, 2015. This is the final and approved form of the dissertation. Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations Jelena Perovanovic Dissertation Research Committee: Eric P. Hoffman, Professor of Integrative Systems Biology, Dissertation Director Anamaris Colberg-Poley, Professor of Integrative Systems Biology, Committee Member Robert J. Freishtat, Associate Professor of Pediatrics, Committee Member Vittorio Sartorelli, Senior Investigator, National Institutes of Health, Committee Member ii © Copyright 2015 by Jelena Perovanovic All rights reserved iii Acknowledgments I am deeply indebted to countless individuals for their support and encouragement during the past five years of graduate studies. First and foremost, I would like to express my gratitude to my mentor, Dr. Eric P. Hoffman, for his unwavering support and guidance, and keen attention to my professional development. This Dissertation would not have been possible without the critical input he provided and the engaging environment he created. -
Ankyrin-G Regulates Neurogenesis and Wnt Signaling by Altering the Subcellular Localization of Β-Catenin
Molecular Psychiatry (2015) 20, 388–397 © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15 www.nature.com/mp ORIGINAL ARTICLE Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin O Durak1,6, FC de Anda1,6,7, KK Singh1,8, MP Leussis2,3,4,9, TL Petryshen2,3,4, P Sklar5 and L-H Tsai1 Ankyrin-G is a scaffolding protein required for the formation of the axon initial segment in neurons. Recent genome-wide association studies and whole-exome sequencing have identified ANK3, the gene coding for ankyrin-G, to be a risk gene for multiple neuropsychiatric disorders, such as bipolar disorder, schizophrenia and autism spectrum disorder. Here, we describe a novel role for ankyrin-G in neural progenitor proliferation in the developing cortex. We found that ankyrin-G regulates canonical Wnt signaling by altering the subcellular localization and availability of β-catenin in proliferating cells. Ankyrin-G loss-of-function increases β-catenin levels in the nucleus, thereby promoting neural progenitor proliferation. Importantly, abnormalities in proliferation can be rescued by reducing Wnt pathway signaling. Taken together, these results suggest that ankyrin-G is required for proper brain development. Molecular Psychiatry (2015) 20, 388–397; doi:10.1038/mp.2014.42; published online 13 May 2014 INTRODUCTION E-cadherin in epithelial cells, and is required, along with β2-spectrin, Genome-wide association studies have identified many genes that for the localization of E-cadherin to cell adhesion sites, where it are associated with a risk for mental disorders, such as bipolar assembles a complex that includes the important Wnt pathway 19 disorder, schizophrenia and autism spectrum disorder (ASD).1–7 component β-catenin. -
DISC1-Binding Proteins in Neural Development, Signalling and Schizophrenia
Edinburgh Research Explorer DISC1-binding proteins in neural development, signalling and schizophrenia Citation for published version: Bradshaw, NJ & Porteous, DJ 2012, 'DISC1-binding proteins in neural development, signalling and schizophrenia', Neuropharmacology, vol. 62, no. 3, pp. 1230-41. https://doi.org/10.1016/j.neuropharm.2010.12.027 Digital Object Identifier (DOI): 10.1016/j.neuropharm.2010.12.027 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Neuropharmacology Publisher Rights Statement: Available under Open Access General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 25. Sep. 2021 Neuropharmacology 62 (2012) 1230e1241 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm DISC1-binding proteins in neural development, signalling and schizophrenia Nicholas J. Bradshaw*, David J. Porteous Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, Midlothian EH4 2XU, UK article info abstract Article history: In the decade since Disrupted in Schizophrenia 1 (DISC1)wasfirst identified it has become one of the most Received 29 October 2010 convincing risk genes for major mental illness. -
Ankyrin-G Induces Nucleoporin Nup358 to Associate with the Axon
© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs222802. doi:10.1242/jcs.222802 RESEARCH ARTICLE Ankyrin-G induces nucleoporin Nup358 to associate with the axon initial segment of neurons Bouchra Khalaf1, Alessandro Roncador1, Francesca Pischedda2, Antonio Casini3, Sabine Thomas4, Giovanni Piccoli2, Michael Kiebler4 and Paolo Macchi1,* ABSTRACT Nup358, also known as Ran-binding protein 2 (RanBP2), is by far Nup358 (also known as RanBP2) is a member of the large nucleoporin the largest nucleoporin with an approximate molecular mass of family that constitutes the nuclear pore complex. Depending on the cell 358 kDa (Bernad et al., 2004; Delphin et al., 1997; Yokoyama et al., ∼ type and the physiological state, Nup358 interacts with specific partner 1995). It harbors several distinct domains: an N-terminus of 700- proteins and influences distinct mechanisms independent of its role in residues, known as the leucine-rich region (LRR), containing a nucleocytoplasmic transport. Here, we provide evidence that Nup358 leucine zipper motif, four homologous RanGTP-binding domains, associates selectively with the axon initial segment (AIS) of mature eight tandem zinc finger motifs, a small ubiquitin-like modifier neurons, mediated by the AIS scaffold protein ankyrin-G (AnkG, also (SUMO) E3 ligase domain, and a C-terminal cyclophilin A known as Ank3). The N-terminus of Nup358 is demonstrated to be homology domain (Wu et al., 1995). Because of this multi-domain sufficient for its localization at the AIS. Further, we show that Nup358 is architecture, Nup358 interacts with specific cellular proteins and expressed as two isoforms, one full-length and another shorter form of consequently triggers a range of downstream effects. -
Structural and Functional Analysis of Translocation in DISC1 Gene and Impact on Schizophrenia
CAPITAL UNIVERSITY OF SCIENCE AND TECHNOLOGY, ISLAMABAD Structural and Functional Analysis of Translocation in DISC1 gene and Impact on Schizophrenia by Jaweria Zia A thesis submitted in partial fulfillment for the degree of Master of Science in the Faculty of Health and Life Sciences Department of Bioinformatics and Biosciences 2021 i Copyright © 2021 by Jaweria Zia All rights reserved. No part of this thesis may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, by any information storage and retrieval system without the prior written permission of the author. ii I dedicate this thesis to my parents and my teachers. CERTIFICATE OF APPROVAL Structural and Functional Analysis of Translocation in DISC1 gene and Impact on Schizophrenia by Jaweria Zia (MBS191024) THESIS EXAMINING COMMITTEE S. No. Examiner Name Organization (a) External Examiner Dr. Mazhar Qayyam PMAS-UAAR, Rawalpindi (b) Internal Examiner Dr. Erum Dilshad CUST, Islamabad (c) Supervisor Dr. Syeda Marriam Bakhtiar CUST, Islamabad Dr. Syeda Marriam Bakhtiar Thesis Supervisor April, 2021 Dr. Sahar Fazal Dr. Muhammad Abdul Qadir Head Dean Dept. of Biosciences & Bioinformatics Faculty of Health & Life Sciences April, 2021 April, 2021 iv Author's Declaration I, Jaweria Zia hereby state that my MS thesis titled \Structural and Func- tional Analysis of Translocation in DISC1 gene and Impact on Schizophre- nia" is my own work and has not been submitted previously by me for taking any degree from Capital University of Science and Technology, Islamabad or anywhere else in the country/abroad. At any time if my statement is found to be incorrect even after my graduation, the University has the right to withdraw my MS Degree.